During the current ICMIC cycle our goal has been to disseminate the principles and mind-set of noninvasive molecular imaging to the UCLA cancer research community, in keeping with the 1999 ICMIC RFA objectives. During the past four years, non-invasive imaging technology in small animal cancer research has permeated the campus. Fostered by the ICMIC, under the umbrella of the UCLA Cancer Center and the Crump Institute for Molecular Imaging, a campus-wide small animal imaging facility has been established. Two years ago we initiated an ICMIC policy to encourage application of molecular imaging technologies to translational studies with clinical endpoints. In the 2004 ICMIC RFA, the NCI has retargeted the ICMIC goals to "capitalize on the extraordinary opportunity for molecular imaging to have an impact on the diagnosis and treatment of cancer patients non-invasively and quantitatively." Research Component 1 of this application is a clinical extension of two of our previous Developmental Projects, to bring reporter gene marked T-cells to clinical trials to monitor TCL targeting to melanoma immunotherapy. Research Component 2 is also an expansion of a previous Developmental Project, to (i) monitor PET metabolic responses to targeted kinase therapies in the clinic and (ii) to develop, with culture and animal models, the optimal use of metabolic imaging to distinguish rapidly responders and non-responders. Research Component 3, an extension of a current Developmental Project, is creating a new non-invasive PET reporter gene mat will have minimal interfering effects and that makes use of positron-labeled reporter probes that are already in clinical trials. Research Component 4 extends to a pre-clinical metastasis model laboratory-based, proof-of principle experiments in monitoring adenovirus redirection and restriction to tumors. Our proposed Developmental Fund projects similarly emphasize translational studies to bring radio-nuclide based molecular imaging, through pre-clinical models, to clinical applications. Research Component projects, Developmental Fund projects and Career Development Award projects are supported by our three continuing Specialized Resources;(i) the Cytrotron and Radiochemistry Specialized Resource, (ii) the Molecular Imaging Specialized Resource and (iii) the Quantitative Image Analysis Specialized Resource. Our goals, through our Research Components, Developmental Fund and Career Development Component will be (i) to continue to foster the incorporation of non-invasive molecular imaging to the best of cancer research at UCLA and (ii) to recruit, encourage and provide resources to encourage translation of molecular imaging principles and practices to cancer diagnosis, management and therapy.